载脂蛋白 E*Ɛ2 携带者在长期服用阿司匹林治疗期间表现出高阿司匹林治疗的血小板反应性和低心血管风险。

Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment.

机构信息

Department of the Eighth Healthcare, Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing 1000853, China.

Department of Urology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Age Ageing. 2022 Jun 1;51(6). doi: 10.1093/ageing/afac119.

DOI:10.1093/ageing/afac119

PMID:35647761

Abstract

OBJECTIVE

Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown.

METHODS

A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded.

RESULTS

After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048-0.715, P = 0.014; HR = 0.435, CI: 0.234-0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers.

CONCLUSIONS

Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.

摘要

目的

载脂蛋白 E（APOE）基因座，包括 rs429358（Ɛ4）和 rs7412（Ɛ2），与心血管（CV）健康有关。然而，它们对阿司匹林的 CV 保护作用的影响尚不清楚。

方法

共招募了 515 名正在服用阿司匹林且存在 CV 疾病的个体，在入组时评估了他们的 APOE 基因型、血小板功能和其他常规实验室参数。记录了平均 5.2 年随访期间的首次主要 CV 事件（心肌梗死、中风、血运重建和 CV 死亡）和所有 CV 事件（主要 CV 事件加不稳定型心绞痛和短暂性脑缺血发作）。

结果

在调整年龄、性别、BMI、生活方式、血脂谱和其他 CV 药物及合并症后，发现Ɛ2 携带者发生主要 CV 的风险降低约 80%，所有 CV 的风险降低 60%（HR=0.186，CI：0.048-0.715，P=0.014；HR=0.435，CI：0.234-0.812，P=0.009），与Ɛ2 非携带者相比。此外，通过花生四烯酸诱导的光传输聚集测定法（23.4%比 13.7%，P=0.038）发现血小板高反应性发生率高、甘油三酯和血红蛋白低、低密度脂蛋白低。与Ɛ4 非携带者相比，Ɛ4 携带者的胆固醇和高胆固醇血症发生率略有增加。

结论

我们的研究结果表明，APOE*Ɛ2 携带者可以从长期阿司匹林治疗中获得额外的 CV 益处。此外，还观察到 APOE2 与环氧化酶-1（COX-1）相互作用并上调其活性。阿司匹林在Ɛ2 携带者中的 CV 保护作用可能归因于 APOE2 上调血管 COX-1 介导的 CV 保护途径，同时阿司匹林部分抑制血小板 COX-1 介导的血小板聚集。